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目的:探讨成纤维细胞生长因子诱导14(Fn14)在表皮生长因子受体(EGFR)外显子19缺失的非小细胞肺癌(NSCLC)组织中的表达及其临床意义。方法:选择2010年9月至2013年11月第四军医大学唐都医院收治的125例原发性EGFR外显子19缺失的NSCLC组织及与之相对应的30例正常肺组织为研究对象,应用免疫组化法检测和比较其Fn14的表达,分析Fn14的表达与原发性EGFR外显子19缺失的的NSCLC临床病理特征的关系。结果:Fn14阳性表达主要定位于胞膜和胞质中。在125例原发性EGFR外显子19缺失的NSCLC组织中,Fn14的阳性表达率为100%,显著高于正常肺组织(P<0.001)。鳞癌和腺癌NSCLC组织中Fn14的阳性表达率比较无统计学差异(P=0.106);不同病理分化程度、不同TNM分期的NSCLC组织中Fn14的阳性表达率比较均具有显著性差异(P=0.000、P=0.000)。Fn14蛋白的表达与EGFR外显子19缺失的NSCLC的淋巴结转移状态、肿瘤大小以及肿瘤解剖学分类均显著相关(P=0.000、P=0.029、P=0.000、P=0.026),而与患者的性别、年龄、吸烟史均无关(P=0.816、P=0.122、P=0.816)。结论:Fn14在原发性EGFR外显子19缺失的NSCLC中呈异常高表达,EGFR外显子19缺失突变很可能通过上调Fn14通路,促进NSCLC的发生和发展。
Objective: To investigate the expression and clinical significance of fibronectin-14 (Fn14) in non-small cell lung cancer (NSCLC) tissues with deletion of exon 19 of epidermal growth factor receptor (EGFR). Methods: From September 2010 to November 2013, 125 cases of primary NSCLC with deletion of exon 19 of 19 EGFR and 30 normal lung tissues corresponding to it were enrolled in this study from Tangdu Hospital of the Fourth Military Medical University. The expression of Fn14 was detected by immunohistochemistry and the relationship between Fn14 expression and the clinicopathological features of NSCLC with deletion of exon 19 of primary EGFR was analyzed. Results: The positive expression of Fn14 mainly localized in membrane and cytoplasm. The positive rate of Fn14 expression was 100% in 125 cases of NSCLC with deletion of exon 19 of EGFR, which was significantly higher than that of normal lung tissue (P <0.001). The positive expression rate of Fn14 in squamous cell carcinoma and adenocarcinoma NSCLC tissues showed no significant difference (P = 0.106). The positive expression rates of Fn14 in NSCLC tissues with different histological grade and TNM stage were significantly different (P = 0.000, P = 0.000). The expression of Fn14 protein was significantly correlated with lymph node metastasis, tumor size and tumor anatomy classification of NSCLC with deletion of EGFR exon 19 (P = 0.000, P = 0.029, P = 0.000, P = 0.026) Sex, age, smoking history were not related (P = 0.816, P = 0.122, P = 0.816). CONCLUSION: Fn14 is highly expressed in NSCLC with deletion of exon 19 of primary EGFR. Exon 19 deletion mutation of EGFR may promote the occurrence and development of NSCLC by up-regulating Fn14 pathway.